NADPH Oxidases as Regulators of Tumor Angiogenesis: Current and Emerging Concepts

Sanja Coso, Ian Harrison, Craig B. Harrison, Antony Vinh, Christopher G. Sobey, Grant R. Drummond, Elizabeth D. Williams, Stavros Selemidis
2012 Antioxidants and Redox Signaling  
Stavros (2012) NADPH oxidases as regulators of tumor angiogenesis : current and emerging concepts. ABSTRACT Significance: Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades to inflict cell damage and to cause cancer by oxidation and nitration of macromolecules including DNA, RNA, proteins and lipids. Recent advances: A current concept suggests that ROS can also promote
more » ... ell signaling pathways triggered by growth factors and transcription factors that ultimately regulate cell proliferation, differentiation and apoptosis, all of which are important hallmarks of tumor cell proliferation and angiogenesis. Moreover, an emerging concept indicates that ROS regulate the functions of immune cells that infiltrate the tumor environment and stimulate angiogenesis, such as macrophages and specific regulatory T cells. Critical Issues: In this review, we highlight that the NADPH oxidase family of ROS-generating enzymes are the key sources of ROS and thus play an important role in redox signaling within tumor, endothelial and immune cells to thereby promote tumor angiogenesis. Future Directions: Knowledge of these intricate ROS signaling pathways and identification of the culprit NADPH oxidases is likely to reveal novel therapeutic opportunities to prevent angiogenesis that occurs during cancer and which is responsible for the revascularization following current anti-angiogenic treatment.
doi:10.1089/ars.2011.4489 pmid:22229841 fatcat:wp3v66lwtfe2pkrb6tyevegbwm